Genetic Variant IGSF23:p.Pro141Thr (chr19-44627449-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001205280.2(IGSF23):c.421C>A(p.Pro141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P141H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGSF23
NM_001205280.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.609

Publications

0 publications found

Variant links:

Genes affected

IGSF23 (HGNC:40040): (immunoglobulin superfamily member 23) This gene encodes a protein that has one immunoglobulin (Ig) domain and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Nov 2011]

IGSF23 links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12759808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205280.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF23	NM_001205280.2	MANE Select	c.421C>A	p.Pro141Thr	missense	Exon 3 of 5	NP_001192209.1	A1L1A6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGSF23	ENST00000402988.6	TSL:3 MANE Select	c.421C>A	p.Pro141Thr	missense	Exon 3 of 5	ENSP00000385592.1	A1L1A6
IGSF23	ENST00000441389.1	TSL:1	c.256C>A	p.Pro86Thr	missense	Exon 2 of 3	ENSP00000407344.1	H0Y6S3
IGSF23	ENST00000911252.1		c.508C>A	p.Pro170Thr	missense	Exon 4 of 6	ENSP00000581311.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688250

African (AFR)

AF:

0.00

AC:

AN:

31570

American (AMR)

AF:

0.00

AC:

AN:

35608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25134

East Asian (EAS)

AF:

0.00

AC:

AN:

35676

South Asian (SAS)

AF:

0.00

AC:

AN:

79038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077474

Other (OTH)

AF:

0.00

AC:

AN:

57886

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.54

M_CAP

Benign

0.011

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.61

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.027

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.15

MutPred

0.22

Gain of phosphorylation at P141 (P = 0.0483)

MVP

0.10

ClinPred

0.95

GERP RS

0.48

Varity_R

0.096

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over